Gynecologic Oncology 138 (2015) 227–234

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Conference Report The American Society of Clinical Oncology 51st Annual Meeting 2015: An overview and summary of selected abstracts Keywords: American Society of Clinical Oncology 2015 Annual Meeting ASCO Gynecologic cancers

1. Introduction On May 29 to June 2, 2015, the American Society of Clinical Oncology (ASCO) held its annual meeting in Chicago, IL, USA. The theme of the meeting this year was “Illumination and Innovation” and the data presented held up to this high aspiration. The main plenary session focused on novel immunotherapy in melanoma, pediatric cancer survivorship, and the cost of new cancer therapy. There were 12 gynecologic oncology abstracts selected for poster discussion and 14 abstracts in gynecologic oncology presented as oral presentations in three different sessions. Three themes emerged from this meeting in relationship to gynecologic cancer, the use of biomarkers for patient selection, the use of antiangiogenesis agents in endometrial cancer, and the evolution of novel immunotherapy agents in gynecologic malignancy. This review will summarize selected studies with further detailed data presented in the tables for all phase II and III study abstracts for ovarian, endometrial, and cervical cancers (Tables 1 and 2). 2. Using biologic markers or phenotypes for patient selection in ovarian cancer Four out of the five ovarian cancer trials presented as oral abstracts focused on the use of biomarkers to evaluate for effect. The first of these was an analysis of the TRINOVA-1 study focusing on a prespecified biologic phenotype of patients with ascites at study entry. TRINOVA-1 was a phase III randomized study of weekly paclitaxel (P) with trebananib (T), an antiangiogenic peptibody that inhibits angiopoietin 1 and 1 binding to the Tie2 receptor, or weekly P with placebo (Abstract 5503). Evaluation of the overall survival (OS) endpoint did not demonstrate statistical significance in the intent to treat population. However, the pre-specified subset of patients with ascites (n = 295) demonstrated a difference in median OS of 2.2 months between patients with ascites receiving T + P vs P alone (14.5 vs 12.3 months; hazard ratio (HR) = 0.72, 95% CI 0.55–0.93; p = 0.011). After on-study progression, 684 (74%) patients received a median of 2 (range, 1–8) additional lines of therapy. Median progression free survival 2 (PFS2) in the T + P arm increased by 1.6 months (12.5 vs 10.9 months with P alone; HR = 0.85, 95% CI 0.74–0.98; p = 0.024). Analysis of time to second subsequent therapy confirmed the PFS2 result (median 13.4 vs 11.7 months with P alone; HR = 0.83, 95% CI, 0.72–0.96; p = 0.012). The incidence of grade ≥ 3 adverse events (AEs) was 60% for T + P vs 56% for P alone. Trebananib + paclitaxel

was associated with more AE-related treatment discontinuations (22% vs 8%) and localized edema events (any grade, 59% vs 27%). These data suggest that for patients with ascites, the addition of T to weekly P seems to improve OS and is well tolerated. The second phase III study presented a comparison of single agent chemother\apy with or without pertuzumab in platinum resistant ovarian cancer patients (Abstract 5504). Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular dimerization domain (Subdomain II) of HER2, and thereby blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3, and HER4. Enrollment criteria included mandatory low tumor HER3 mRNA expression by central laboratory testing with the goal to select patients most likely to respond to pertuzumab. This is one of the first phase III studies in ovarian cancer to use a biomarker for enrollment. Investigators were given a choice of gemcitabine, P, or topotecan as chemotherapy and patients were stratified by chemotherapy backbone, prior antiangiogenic therapy, and platinum free interval (b3 vs 3–6 months). The patients were then randomized to chemotherapy +/− pertuzumab. One hundred and fifty six patients were randomized, but only 207 were eligible out of the 324 patients who were screened for HER3 expression. The addition of pertuzumab to chemotherapy improved PFS (median 4.3 months vs 2.6 months for placebo + chemotherapy); but did not reach statistical significance. Subgroup analyses by chemotherapy type showed trends of improvement in PFS with the addition of pertuzumab in the gemcitabine and P arms, but no improvement in the topotecan arm. Although the primary objective was not met, subgroup analyses showed trends favoring pertuzumab in two of the chemotherapy cohorts. These results merit further exploration. Two phase II studies using TP53 mutation screening were presented. Both of these studies used a novel Wee 1 inhibitor, AZD1775 in combination with chemotherapy. AZD1775 is a small molecule Wee1 inhibitor and is predicted to sensitize TP53 mutant tumors to genotoxic agents such as platinum chemotherapy through deregulation of the G2/M checkpoint (Abstract 5506). The first of these studies presented was a phase II study of platinum sensitive ovarian cancer patients screened for TP53 mutation treated with AZD1775 and carboplatin (C) and P. Patients received AZD1775 or placebo BID for 2.5 days plus P (175 mg/m2; IV) and C (AUC5; IV) on day 1 per 21-day treatment cycle, until progression or the completion of 6 cycles. Primary objectives were PFS by enhanced or volumetric RECIST 1.1 and safety and tolerability. Secondary objectives were overall response rate (ORR), PFS by standard RECIST 1.1, and OS. Only 53% of women had TP53 mutations that met the criteria for enrollment and 121 patients were randomized. Progression free-survival by independent central review (~ 57% maturity) was significantly greater with AZD1775/P/C compared with P/C alone with median 42.86 vs 34.86 weeks. Overall response rates were 81.4% vs 75.8% and not statistically significantly different with AZD1775/P/C vs P/C, respectively. Overall survival data are immature. Most common AEs were nausea, diarrhea, alopecia, and fatigue. Similar proportions of patients discontinued therapy due to toxicity between the groups (20.3% vs 21.7). Overall the combination of


Conference Report

AZD1775/P/C was associated with a significant increase in PFS when compared with P/C alone, met the preset primary and secondary PFS goals for clinical importance, and showed acceptable tolerability in women with TP53-mutant ovarian cancer. The second AZD1775 study included the same TP53 inclusion criteria but focused on a primary platinum resistant ovarian cancer cohort with either recurrence in 3 months or less from primary treatment or platinum refractory disease (Abstract 2507). This study enrolled 22 women with the above criteria to C AUC 5 with the addition of AZD1775 on days 1–3 of a 21 day cycle. Of note, all patients had prior debulking surgery and only one line of prior therapy. Toxicity was acceptable with 17% grade 3 thrombocytopenia and 9% grade 3 neutropenia. The ORR was 41% with 1 complete response, 8 partial responses, and 8 patients with stable disease. Two patients have ongoing responses for over 3 years. The median PFS is 4.5 months. Platinum refractory patients tended to not respond to this therapy. These data strengthen the concept of biomarker directed therapy and the role of TP53 mutations in ovarian cancer. The phase II study, ARIEL 2 (Part 1), designed to prospectively identify platinum sensitive, recurrent ovarian cancer patients most likely to respond to rucaparib, a PARP inhibitor (Abstract 5508). While it appears that at least 50% of ovarian cancers have some homologous recombination deficiency (HRD) it remains unclear which of these deficits will predict response to PARP inhibition. Investigators in this study tested a novel next generation sequencing-based HRD assay and algorithm to predict rucaparib sensitivity by assessing tumor BRCA status and genome-wide loss of heterozygosity (LOH). ARIEL2 (Part 1) enrolled women with platinum-sensitive, recurrent, high-grade serous, or endometrioid ovarian cancer. The primary objective was to evaluate rucaparib activity in tumor BRCA mutation (BRCAmut), BRCA wildtype with LOH-high (BRCAwt/LOHhigh), and BRCA wildtype with LOH low (BRCAwt/LOHlow) (biomarker negative group). Overall response rates of 69%, 39%, and 11% in BRCAmut, BRCAwt/LOHhigh, and BRCAwt/LOHlow patients were demonstrated, respectively (p b 0.0001). This study represents an advance in the ability to use ovarian cancer tumor characteristics to predict response to PARP inhibition. Lastly, a novel folate receptor targeting agent conjugated to a potent maytansinoid, IMGN853, was described in two phase I studies (Abstracts 5518 and 5558). Patients with folate receptor positive platinum resistant ovarian or relapsed/refractory endometrial cancer were eligible. Toxicity was generally grade 1 or 2 with diarrhea, ocular events, cough, fatigue, neuropathy, and nausea. In the first phase 1 study, 14 patients with platinum resistant ovarian cancer were treated. There were 4 partial responses and 1 confirmed CA-125 response in 10 evaluable patients with an ORR of 40% and a clinical benefit rate of 50%. The second phase 1 study enrolled 59 patients with folate receptor positive tumors with clinical benefit seen in both epithelial and transitional cell ovarian cancer. These results suggest a promising effect with this novel targeted agent. 3. Antiangiogenesis inhibition in endometrial cancer The use of the antiangiogenesis agent, bevacizumab was highlighted in two oral presentations, both with positive results. The first was the much-anticipated results of Gynecology Oncology Group (GOG) protocol 086P (Abstract 5500). This study was a three arm phase II randomized study of chemotherapy naïve, recurrent, or advanced endometrial cancer patients utilizing novel agents. Arm 1 was C/P + bevacizumab for 6 cycles followed by bevacizumab maintenance until progression or toxicity. Arm 2 was C/P + temsirolimus for 6 cycles followed by temsirolimus maintenance. Arm 3 was C/ixabepilone + bevacizumab for 6 cycles followed by bevacizumab maintenance. Adverse events leading to discontinuation were similar (25%) in all arms. Fistula or perforation rate was 2–4% in all arms. Overall response rate was 45–50% in all arms comparable with GOG 209 historical reference ORR = 51%. Progression free survival was not significantly increased in any

experimental arm (p N 0.039) when each arm was compared to historical control. Hazard Rate (92% CI) for arms 1, 2, and 3 was 0.81 (0.63– 1.02), 1.22 (0.96–1.55), and 0.87 (0.68–1.11), respectively. Overall survival at 36 months, a secondary endpoint, was statistically significantly increased in arm 1 (C/P + bevacizumab) relative to control but was not significantly increased in arms 2 or 3 (HR (92% CI) arms 1, 2, and 3 was 0.71 (0.55–0.91), 0.99 (0.78–1.26), and 0.97 (0.77–1.23)). The median OS of 34 months in arm 1 was compared with 22 months in GOG 209. The second study was a randomized phase II study C and P versus C/ P + bevacizumab in advanced or recurrent endometrial cancer patients (Abstract 5502). Patients could have received on prior line of platinum based chemotherapy but could not have progression b 6 months from completion. Type 1 and 2 endometrial cancers were eligible. Of 108 patients enrolled, 66% had recurrent disease, 60% had type 1 histology and 55% were grade 3. Vascular comorbidity was present in 57%. Progression free survival was increased in the bevacizumab containing arm to 13.0 months compared with 8.7 months in the control arm (p = 0.036). The ORR was also improved to 72.7% vs 54.3%. The OS data is not yet mature. There was more cardiac toxicity in the bevacizumab containing regimen with 4 cases of grade 3 cardiac toxicity versus 0 in the control. There were also significantly more thromboembolic events in the bevacizumab containing arm including 3 deep vein thrombosis, 3 retinal artery thrombosis, 2 intracardiac thrombus, 1 silent myocardial infarction, and 1 stroke. The investigators suggest careful evaluation of pre-existing cardiac risk factors in this older patient population. 4. Immunotherapy in gynecologic cancer Immunomodulation with novel agents such as CTLA-4 inhibitors (ipilumimab), PD1, and PDL-1 inhibitors made a huge contribution to the meeting this year. The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against multiple cancers. Three abstracts were presented which demonstrated the use of some of these agents in gynecologic cancer. The first was an ongoing phase Ib study of Avelumab, a fully humanized anti PD-L1 IgG, in 75 recurrent and refractory ovarian cancer patients (Abstract 5509). A dose of 10 mg/kg was decided from the phase Ia dose escalation portion although no maximum tolerated dose (MTD) was obtained. Patients had a median of 4 prior lines of therapy and no PD-L1 expression was required for entry. Two patients had clear cell carcinomas and 70% had serous histology. There were only 8% grade 3 treatment related AEs and no grade 4 toxicities or deaths. There were no complete responses but 10.7% of patients had a partial response and 44% with stable disease. Median duration of response is 21 weeks but 5 patients are still responding to therapy. Of note, both of the patients with clear cell histology responded to treatment. This study represents that largest group of ovarian cancer patients treated with an anti-PD-L1 antibody. The next abstract is a phase I study of pembrolizumab, a human monoclonal antibody against PD-1 evaluated in a cohort of advanced ovarian cancer patients (Abstract 5510). This study preselected patients who had PD-L1 expression in ≥ 1% of cells in tumor nests or PD-L1+ bands in stroma as determined by a prototype IHC assay at a central laboratory. Grade 3–4 AEs were uncommon with only one case of elevated transaminases, but 69% of patients had some AE, mostly arthralgias, hyper, or hypothyroidism. The best ORR was 11.5% and included 1 complete response, 2 partial responses, and 6 patients with stable disease in a cohort of 26 patients. Responses were very durable over several months and at least 1 year in 1 patient thus far with median response duration not reached at this time. There were no discontinuations for toxicity. Lastly, the third abstract described the long-term outcomes of ovarian cancer patients treated in a phase II study with nivolumab (Abstract 5570). Nivolumab is a fully humanized IgG4 that blocks the engagement of PD-1 by PD-L1. The investigators previously showed that nivolumab

Table 1 Phase II trials of novel agents and cytotoxic treatment strategies in ovarian, fallopian tube, and primary peritoneal carcinomas. Trial type

Abs no.



Phase II single agent


Rucaparib (600 mg BID), 21-day cycle

Poly(ADP-ribose) polymerase (PARP) Relapsed gBRCAmut high-grade EOC/FTC/PPC, 2–4 prior ct inhibitor regimens, PFI ≥ 6 mo from last pt dose; ECOG PS 0–1 (n = 35)


Belotecan (0.5 mg/m2) vs. topotecan (1.5 mg/m2), 5 days, q3w, 6 cycles

Camptothecin-derived topoisomerase I inhibitors

Olaparib (400 mg BID)

Poly(ADP-ribose) polymerase (PARP) gBRCAmut OC (n = 167; inhibitor (A) b3 prior lines of ct n = 30, (B) ≥3 prior lines of ct n = 137)


Type of patients

Recurrent/refractory OC (n = 141, FA = 140, PP = 130)

Selinexor (50 mg/m2 BIW, 35 mg/m2 BIW, or 50 mg/m2 qw in 4 week cycles)

Inhibitor of XPO1-mediated nuclear export, resulting in nuclear retention and activation of multiple tumor suppressor proteins

Advanced/metastatic OC/EC/CC; ≥1 prior lines of ct (n = 63)


Multiple peptide vaccine (OC = FOXM1, MELK, HJURP, HIG2, VEGFR1/2; CC = FOXM1, MELK, HJURP, URLC10, HIG2) (mixed 1 mg with 1 mL of adjuvant, montanide, ISA51), 12 subcutaneous injections, qw, + additional administrations

Immunotherapy using human leukocyte antigen-restricted tumor specific epitope peptide and VEGFR1/2

Heavily treated/treatment-resistant OC/CC; HLA-A2402 or A0201 within PS2 (n = 67)


Olaparib (150 mg BID, days 1–3, qw) + C/P (AUC2/60 mg/m2, qw, 3 weeks of 4), transitioned to Olaparib (300 mg BID) with confirmed complete remission


p-Value Major toxicity

0.69/ 0.68 0.60 0.53

0.645 0.499 NS NS 0.053 0.023

n (55%), f (51%), An (31%), Gr ≥3 An (19%), serious AE (10%), leukemia (1%), myelodysplastic syndrome (b1%) (n = 193 for safety/tolerability profile)

Gr3 AEs: n (13%), PLTS (13%), v (11%), f (10%); Gr1/2 AEs: n (54%), v (5%), f (32%), anorexia (25%); dose-reduction in 30% pts No major AEs; most pts developed specific CTL responses

mo, (B) 8.0 mo Plt-Ref ORR: (A) 0%, (B) 14% Plt-Ref Mean DoR: (A) 0 mo, (B) 6.4 mo – Evaluable ORR — (OC) 9%, (EC) 18%, CC 7% Evaluable DCR — (OC) 36%, (EC) 64%, (CC) 28% – CR (RECIST) — 2 (3%) Median OS — (OC) 8.8 mo, (CC) 15.4 mo Lower CRP levels (b2.0

(Generally Gr1/2): n (55%), An (41%), ALT/AST elevation (41%), f (41%), asthenia (35%)

Gr3/4 AEs same between both arms

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Results ORR — (RECIST/CA-125) 81%, (RECIST) 65%, (PFI 6–12 mo) 88%, (PFI N12 mo) 56%, RECIST response — (≥3 prior ct regimens) 58% ORR by RECIST/GCIG — (FA) 29.6 vs. 26.1% (PP) 30.3 vs. 25% PFS by NCI-CTCAE — (FA/PP) 26.4 vs. 17.3 mo OS by NCI-CTCAE — (FA) 37.1 vs. 21.3 mo (PP) 37.1 vs. 24.9 mo Total ORR: (A) 47%, (B) 34% Total Mean DoR: (A) 6.2 mo, (B) 7.9 mo Plt-S ORR: (A) 67%, (B) 45% Plt-S Mean DoR: (A) 5.7 mo, (B) 8.2 mo Plt-Res ORR: (A) 50%, (B) 29% Plt-Res Mean DoR: (A) 8.3

0.0016 b.0001 0.065

mg/dL) had longer median OS — (OC) 3.0 mo, (CC) 19.0 mo Median OS in DHT — vs. +

Poly(ADP-ribose) polymerase (PARP) Measurable disease, adequate inhibitor organ function, ECOG PS ≤2, failed 1st-line pt-containing ct (n = 54)

pts: (OC) 1.4 vs. 17.7 mo, (CC) 3.3 vs. 21.2 mo CR — 22.5%, all alive PR — 30% SD — 25% PD — 22.5% 6/9 CRs were gBRCAmut Median PFS — (gBRCAmut) 19 vs. 4 mo (non-gBRCAmut)

1 Gr4 ANC and allergic reaction to C; common Gr3 AEs: ANC, An, PLTS; 2 mild GI toxicities


(continued on next page)


Table 1 (continued) Trial type

Abs no.



Type of patients



p-Value Major toxicity



Nab-paclitaxel followed by GM-CSF

Temsirolimus (15 mg/m2) + Trabectedin (0.15 mg/m2), qw for 3 weeks, 1 week rest

Cytotoxic; antitumor immune response

mTOR inhibitor; binder to the DNA minor-groove

e16575 Metronomic cyclophosphamide (50 mg, qd at 10 am) + temozolomide (20 mg BID, days 1–14), repeated q3w



Bevacizumab (2 mg/kg) + eribulin (1 mg/m2) + oxaliplatin (30 mg/m2), 3 weeks, 1 week rest, q 4 weeks

Anti-VEGF antibody; Halichondrin B analog with mitotic spindle disruption; cytotoxic

AZD1775 (225 mg BID, 2.5 days) + C/P (AUC5/175 mg/m2, day 1) vs. C/P alone, 21-day cycle

Wee1 G2 checkpoint Ser/Thr protein kinase inhibitor; cytotoxic

5506 Randomized Phase II combination

TP53-mutant Pt-S OC (n = 121)

PFS — (enhanced RECIST) 34.14 vs. 31.86 weeks; (RECIST) 42.86 vs. 34.86

– 0.0035 0.003 0.0544

No toxicities NGr2

0.63 0.55

0.080 0.030

Grade 3/4 AEs: ANC (20%), leucopenia (59%), PLTS (22%), anorexia (17%), rash (7%); hematological toxicity mostly transient; 1 ≥Gr3 febrile ANC Gr3/4 hematological AEs in 4 pt (13%); Gr3 hypoalbuminemia and edema in 1 patient (3%), respectively; no significant difference in serum VEGF level n (78 vs. 60%), d (74.6 vs. 36.7%), alopecia (54.2 vs. 66.7%), f (54.2

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Median OS — (gBRCA ) 24 vs. 16 mo (non-gBRCAmut) Median OS — 16.8 mo Recurrent Pt-R OC/FTC/PPC, Mean TTP — 5.5 mo (pts average of 3 prior lines of ct, with 52% received bevacizumab CR) vs. 4.5 mo (no CR) (n = 21) ORR — 71% CR — 29% PR — 43% Response against IGF1R and fold change correlated to TTP MDSC levels at enrollment associated with CR CR — 1 (5%) ECOG PS = 0–2, histologically PR — 2 (10%) confirmed ovarian clear cell SD beyond 3 mo — 6 (29%) adenocarcinoma, Pt-R OC CBR — 43%, median DoR (n = 21) 3.5 mo No difference in serum VEGF Pt-R OC, histologically proven CR — 0 (n = 55) PR — 24 ORR — 44.4% Median PFS — 5.9 mo Median OS — 10.1 mo 1 yr survival rate — 33% ECOG PS = 0–2, Pt-R, histologically CR — 2 (7%) PR — 5 (17%) confirmed EOC SD — 15 (50%) (n = 30) RR — 23% CBR — 73% Median PFS — 3 mo


weeks ORR — 81.4 vs. 75.8% Best (CA-125) RR — 81.35 vs. 74.19% 5528


C/P (AUC5/6,175 mg/m2) alone (Arm A) or with (Arm C) bevacizumab (15 mg/kg) vs. oxaliplatin (130 mg/m2) + capecitabine (850 mg/m2 BID, days 1–14) alone (Arm B) or with (Arm D) bevacizumab (15 mg/kg), followed by bevacizumab alone, 3-weekly for 12 more cycles; 21-day cycle, 6 cycles NA C/P (AUC6, 175 mg/m2, triweekly, 4 courses) alone or with bevacizumab (15 mg/kg, q3w, ≥3 courses), followed by IDS with C/P +

Cytotoxic; anti-VEGF antibody; cytotoxic

Cytotoxic; anti-VEGF antibody

bevacizumab + 15-month maintenance bevacizumab


EP-100 (30 mg/m2, BIW) + paclitaxel (80 mg/m2, qw) vs. paclitaxel alone (80 mg/m2)

Synthetic cytolytic peptide conjugated to Luteinizing Hormone Releasing Hormone; cytotoxic

Recurrent/advanced mEOC, ct-naïve (n = 50)

CR/PR: (A) 2, (B) 2, (C) 4, (D) 2 Median PFS — (B + D vs. A + C) 10.1 vs. 15.4 mo (C + D vs. A + B) 17.4 vs. 8.8 mo No difference in CRR (1 vs. High-grade serous/endometrioid 0) EOC, FIGO stage III–IV, ECOG 0–2, considered unresectable with NA ct Surgical feasibility rate — 64 vs. 88% and IDS planned (n = 64) Optimal surgery rate — 77.7 vs. 86.4% Pt deemed unresectable at surgery — 2 vs. 0 ORR — 34.8 vs. 33.3% Advanced OC; unlimited prior DCR — 73.9 vs. 71.4% regimens allowed; central IHC for 10 pts progressed on P alone tumoral LHRH receptors required N3 mo SD — 50%, TTP 3–7 (n = 44)

1.08 0.88

0.83 0.72

All NS

Serious Gr3/4 AEs (40.6 vs. 18.8%, p = 0.055), 1 Gr3 entero-vaginal fistulae, 1 surgical dehiscence, 1 DVT

Gr3/4 AEs (43.5 vs. 47.6%, primarily GI and related to underlying disease); infusion-related reactions of all grades (52 vs. 23.8%), EP-100 did not complicate AE profile and was well tolerated

BID = twice daily; BIW = twice weekly; C/P = carboplatin + paclitaxel; Ser = serine; Thr = threonine; v = vomiting; OC = ovarian cancer; EC = endometrial cancer; CC = cervical cancer; PFS = progression-free survival; ORR = objective/overall response rate; n = nausea; d = diarrhea; f = fatigue; AE = adverse event; Gr = grade; WDAE = withdrawal due to adverse events; Pt-S = platinum-sensitive; Pt-R = platinum-resistant; Pt-Ref = platinum-refractory; Pt-Unk = platinum-status unknown; gBRCAmut = germline BRCA mutations; EOC = epithelial ovarian cancer; FTC = fallopian tube cancer; PPC = primary peritoneal cancer; ct = chemotherapy; PFI = progression-free interval; pt = platinum; ECOG PS = Eastern Cooperative Oncology Group Scale of Performance Status; An = anemia; AST = aspartate transaminase; ALT = alanine transaminase; qnw = every n weeks; FA = full analysis; PP = per protocol; OS = overall survival; LHRH = Luteinizing Hormone Releasing Hormone; IHC = immunohistochemistry; mEOC = mucinous epithelial ovarian cancer; CR = complete response; PR = partial response; ANC = neutropenia; htn = hypertension; DoR = duration of response; FIGO = International Federation of Gynecology and Obstetrics; NA = neoadjuvant; IDS = interval debulking surgery; DVT = deep vein thrombosis; DCR = disease control rate; PLTS = thrombocytopenia; HLA = human leukocyte antigen; DTH = dermatological hypersensitivity; CRP

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mo, 1 PR 3/5 pts had 3× NTTP with combo than with P alone

vs. 55%); ≥Gr3 (78 vs. 65%, n = 85), serious AEs (40.7 vs. 20%, n = 36), WDAE (20.3 vs. 21.7%, n = 25) Gr3/4 AEs (most common were ANC + htn for bevacizumab) seen in (A) 62%, (B) 62%, (C) 55%, (D) 92% of pts; Gr4 in 4 pts

= c-reactive protein; CTL = cytotoxic T lymphocyte; qn = every night; HSR = hypersensitivity reactions; PD = progressive disease; SD = stable disease; GM-CSF = Granulocyte-Macrophage Colony-Stimulating Factor; TTP = time to progression; IGF1R = insulin-like growth factor 1 receptor; MDSC = myeloid-derived suppressor cells; QTc = correct QT interval; CNS = central nervous system; HEC = highly emetogenic chemotherapy.



Trial type

Abs no. Agents/dose


Type of patients

Phase II single agent


PI3K inhibitor

Median PFS — 4.5 mo, Histologically-confirmed (low-grade) 8.3 mo, advanced/recurrent EC, ≤1 prior ct regimen (n = 40) (high-grade) 3.8 mo PFSN2 mo — 70% in high-grade strata PFSN3 mo — 57% in low-grade strata ORR — 0% ORR — 0% Histologically confirmed, SD — 38.1% recurrent/persistent uterine leiomyosarcoma, ≥18 years, 1–2 PD — 57.1% Median PFS — 1.7 mo prior ct regimens, measurable Median OS — 14.5 mo disease by RECIST (n = 21) EFS at 6 mo — 0% Persistent/recurrent CC; 1 prior PFS ≥ 6 mo — 5 (18%) ct regimen; measurable disease; PR — 2 (7%) with duration of 8 and 17 mo GOG PS ≤2 (n = 28) SD — 12 (43%) Median PFS — 3.2 mo Median OS — 8.6 mo CR — 76.5% FIGO stages III–IVA Median DoF/U — 27 mo uterine/cervical cancer, 2 yr PFS rate — 83.8% no para-aortic Pelvic disease lymphadenopathy (N10 mm) progression-free rate — assessed by CT (n = 68) 89.6% 2 yr OS rate — 92.7% Locally advanced CC; RR — 96% pathological findings CR — 27%

BKM120 (100 mg, qd), high toxicity led to 60 mg qd

e16512 Alisertib

Aurora A kinase inhibitor

e16599 Brivanib (800 mg) qd, 28-day cycle

Multi-targeted tyrosine kinase inhibitor against VEGF and FGFR

Phase II 5587 combination

Concurrent chemoradiotherapy (EQD2 = 62–65 Gy at point A) + cisplatin (30 mg/m2)/paclitaxel (50 mg/m2)

e16515 Dose-dense paclitaxel (80 mg/m2 days 1,8,15, 3 cycles) + cisplatin (75 mg/m2) day 1), q3w,

Radiation therapy; cytotoxic





Major toxicity

Gr3/4 AEs: cutaneous rash (54%), depressive events (47%), and anxiety (40%); Gr3/4 87% in dose-reduction group; Gr≥ 3 AEs: cutaneous (13%), increased ALT (13%), HTA (17%), hyperglycemia (17%) and increased AST (21%); 5 pts (21%) stopped for toxicity

≥Gr3 AEs: An (4), leukopenia (5), ANC (7), PLTS (1), mucositis (4), d (1), and palmer-planter syndrome (2)

Gr3 AEs: htn (4), An (3), hyponatremia (3), hyperglycemia (2), elevated liver enzymes (2), n (2), h (2), colon hemorrhage (1); Gr4 sepsis (1), htn (1)

2 yr cumulative late complication rates (25% all grades): Gr1 (13.2%), Gr2 (5.9%), Gr3 (2.9%), Gr4 (2.9%)

Gr3/4 AEs: ANC (21%), An (6%), n (4%), f (4%), peripheral sensory neuropathy

Conference Report

Table 2 Phase II trials of novel agents and cytotoxic treatment strategies in endometrial, uterine, and cervical carcinomas.

before surgery + 2 cycles Dose-dense paclitaxel after surgery, if certain pathological findings exist

Randomized 5500 Phase II combination

C/P + bevacizumab (Arm 1) vs. C/P + temsirolimus (Arm 2) vs. ixabepilone + carboplatin + bevacizumab (Arm 3)

Cytotoxic; anti-VEGF antibody; mTOR inhibitor; cytotoxic

Cytotoxic; anti-VEGF antibody


C/P (standard dose, 6-8 cycles) vs. C/P (standard dose, 6–8 cycles) + bevacizumab (15 mg/kg) with maintenance


C/P (AUC5/175 mg/m2, d1q21), 6 cycles + Cytotoxic; anti-EGFR cetuximab (400 mg/m2 1 week before starting monoclonal antibody C/P, then 250 mg/m2, qw) vs. C/P alone (AUC5/175 mg/m2, d1q21), 6 cycles

after surgery include: pelvic lymph node metastases, parametrial invasion, or intrauterine lymphovascular invasion (n = 52) Advanced EC; no prior ct (n = 329)

Advanced (stages III–IV) or recurrent (progression N6 mo after completion of previous pt-based ct) EC; ≤1 prior ct lines; measurable/evaluable disease and both type 1/2 EC eligible (n = 108) Advanced/recurrent CC, b2 previous ct regimens, ECOG PS ≤1 (n = 108)

PR — 69% pCR — 21%

(2%), hyponatremia (2%); 1 Gr5 cardiac arrest, likely unrelated

PFS – not sig increased in any experimental arm vs. control OS 36 mo — increased in arm 1 0.57 No differences in clinico-pathological feature according to arm allocation Median DoF/U — 13 mo ORR — 54.3 vs. 72.7%

At Median DoF/U — 23 mo: 102 had event 97 progressed 61 died Median EFS — 6.0 vs. 4.7


Gr3/4 htn more common in bevacizumab arms than temsirolimus 0.039 pb0.039 (16 vs. 3%, p = 0.001); pneumonitis (p = 0.004) and mucositis (p b 0.001) more common in temsirolimus arm 0.036 Gr3 cardiac toxicity in 4 cases (Arm B) vs. no cases (Arm A); 13 serious AEs in 8 pts: DVT (3), retinal artery thrombosis (3), intracardiac thrombus (2), silent myocardial infarction (1), cerebrovascular accident (1)

– 0.043 0.20 0.27 0.63

No difference in occurrence of severe AEs, except Gr3/4 skin toxicity reported in C/P + cetuximab (8 cases, 6 with acneiform rash, p = 0.004)

mo Median PFS — 7.6 vs. 5.2

mo ORR — (RECIST) 38 vs. 43% EC = endometrial cancer; htn = hypertension; PFS = progression-free survival; ct = chemotherapy; C/P = carboplatin + paclitaxel; DoF/U = duration of follow-up; ORR = overall response rate; DVT = deep vein thrombosis; CR = complete response; OS = overall survival; AST = aspartate transaminase; ALT = alanine transaminase; APRpos = activated progesterone receptor; SD = stable disease; PD = progressive disease; An = anemia; ANC = neutropenia; PLTS = thrombocytopenia; d = diarrhea; CC = cervical cancer; pCR = pathologic complete response; f = fatigue; An = anemia; n = nausea; EFS = event-free survival; VEGF = vascular endothelial growth factor; EGFR = endothelial growth factor receptor; FGFR = fibroblast growth factor receptor; h = headache.

Conference Report

mo Median OS — 17.0 vs. 17.7



Conference Report

can mediate tumor regression in a substantial proportion of patients with ovarian cancer in the study. How long these responses last was unknown. Of the 20 patients with platinum-resistant ovarian cancer treated with nivolumab on the study, 2 had a complete response and one had a partial response and were followed until progression. The two complete responders survived without progression for 17 and 14 months respectively. The responses in these patients lasted for 6 and 3 months after stopping nivolumab. The patient with a partial response survived without disease progression for 5 months. Taken together with the other abstracts presented in immunotherapy in ovarian cancer, these immunotherapy agents appear to generate some profound responses. Further work in determining biomarkers to identify patients who will benefit from the drugs and determining which drugs should be used in combination or in sequence will be vital to eliminating this cancer as a threat to women. 5. Summary In conclusion, the 2015 Annual Meeting of ASCO showed promising results in the utilization of biomarkers to predict response to therapy, immune checkpoint inhibition to produce prolonged responses and antiangiogenesis agents in gynecologic malignancy. Conflict of interest statement Dr. Monk discloses that his institution has received research grants from Novartis (CBKM120C2201), Amgen (20090508), Lilly (NCT01663857), Genentech (NCT01995188), Janssen/Johnson & Johnson (NCT01846611), Array (NCT01849874) and TESARO

(NCT01847274). Dr. Monk has received honoraria for speaker bureaus from Roche/ Genentech, AstraZeneca, and Myriad. Additionally, Dr. Monk has been a consultant for Roche/Genentech, GlaxoSmithKline, Merck, TESARO, AstraZeneca, Gradalis, Advaxis, Verestem, Cerulean, Amgen, Vermillion, ImmunoGen, and Pfizer. Dr. Rimel discloses that she is on the advisory board for AstraZeneca. Steven Gibson has no conflicts of interest to disclose.

Acknowledgment The authors would like to thank Daniele A. Sumner, BA for her assistance in editing the manuscript. The authors are solely responsible for the preparation and content of the manuscript. B.J. Rimel Division of Gynecologic Oncology, Cedars-Sinai, Los Angeles, CA, USA Steven J. Gibson University of Arizona, Tucson, AZ, USA Bradley J. Monk Division of Gynecologic Oncology, Cedars-Sinai, Los Angeles, CA, USA Corresponding author at: University of Arizona Cancer Center, Creighton University School of Medicine at Dignity Health St. Joseph's Hospital and Medical Center, 500 W. Thomas Road, Suite 600, Phoenix, AZ 85013, USA.

The American Society of Clinical Oncology 51st Annual Meeting 2015: An overview and summary of selected abstracts.

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